Evidence from laboratory and small clinical trials has raised the possibility of a benefit of aspirin in the prophylaxis of migraine headaches. Two large-scale randomized trials, the Physicians' Health Study and the British Doctors' Trial, provided clear evidence of a 20% to 30% reduction in rate of recurrence. Neither trial, however, was able to collect detailed information on the type, frequency, severity or duration of the migraine, and both were conducted in men. We have the unique opportunity to evaluate the role of low-dose aspirin in the prophylaxis of migraine headaches in women in a substudy of the Women's Health Study, a very large-scale randomized trial funded by NIH. The Women's Health Study is an ongoing randomized, double-blind, placebo- controlled trial of the balance of benefits and risks of low-dose aspirin (100 mg every other day), beta carotene and vitamin E in the primary prevention of cardiovascular disease and cancer in women over age 45. Participants who report at baseline a history of migraine at least once per month have been invited to joint the migraine substudy. As part of this substudy already in progress, each woman completes a detailed baseline migraine questionnaire, a year of monthly migraine diaries, and a 12-month migraine follow-up questionnaire, to document the existence and type of migraine at baseline, as well as frequency, severity, and duration for the first year after randomization. Information on potential confounders and effect-modifiers, such as use of post menopausal hormones, is obtained as part of the Women's Health Study. To date, over 28,000 female health professionals have been randomized into the Women's Health Study, with 600 currently in the migraine substudy; by the end of enrollment for the Women's Health Study (late 1994/early 1995) approximately 40,000 women will have been randomized into the trial, with approximately 1,000 in the migraine substudy. Thus, the strengths of this substudy compared to other studies to date, relate to the large sample size, as well as the detailed diaries collected at baseline and over a one-year period.